SpringerLink
Log in

Osteoblast Dysfunction in Male Idiopathic Osteoporosis

  • Laboratory Investigations
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

The etiology of primary osteoporosis in young and middle-aged men is unknown. We have studied osteoblast function in cells derived from men with idiopathic osteoporosis and in control cells from age-matched men with osteoarthrosis. Osteoblasts were isolated from transiliac bone biopsies. Osteoblast function was measured as vitamin D-stimulated osteocalcin production and production of cytokines and factors involved in osteoclast activation and bone formation. Cell proliferation was measured as 3H-thymidine incorporation. Parathyroid hormone-related peptide (PTHrP) mRNA was measured using reverse-transcriptase polymerase chain reaction. In osteoporotic men, bone mineral density at the femoral neck was correlated to in vitro production of osteocalcin. Osteoblasts from osteoporotic men produced significantly less osteocalcin after vitamin D stimulation but had increased production of macrophage colony-stimulating factor (M-CSF) compared to controls. The osteocalcin response was negatively correlated to production of M-CSF, interleukin-6, and C-terminal propeptide of type I collagen. Basal 3H-thymidine incorporation was similar in cells from osteoporotic patients and controls. PTHrP (10−9 M) significantly increased cell proliferation in control cells but not in osteoporotic cells. Basal PTHrP mRNA levels were significantly higher in osteoporotic cells than in cells from controls. The results are in agreement with previous histomorphologic studies indicating that men with idiopathic osteoporosis have an osteoblast dysfunction with decreased osteocalcin production and increased production of factors stimulating osteoclast activation. This indicates a catabolic cellular metabolic balance leading to negative bone turnover, resulting in osteoporosis. The cause of such cellular dysfunction needs further evaluation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Chavassieux P, Meunier PJ (2001) Histomorphometric approach of bone loss in men. Calcif Tissue Int 69:209–213

    Article  CAS  PubMed  Google Scholar 

  2. Khosla S, Melton JL III, Atkinson AT, O´Fallon WM, Klee GG, Riggs LB (1988) Relationship between serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab 83:2266–2274

    Google Scholar 

  3. Resch H, Pietschmann P, Woloszczuk W, Krexner E, Bernecker P, Willvonseder R (1992) Bone mass and biochemical parameters of bone metabolism in men with spinal osteoporosis. Eur J Clin Invest 22:542–545

    CAS  PubMed  Google Scholar 

  4. Pietschmann P, Kudlacek S, Grisar J, Spitzauer S, Woloszczuk W, Willvonseder R, Peterlik M (2001) Bone turnover markers and sex hormones in men with idiopathic osteoporosis. Eur J Clin Invest 31:444–451

    Article  CAS  PubMed  Google Scholar 

  5. Byers RJ, Hoyland JA, Braidman IP (2001) Osteoporosis in men: a cellular endocrine perspective of an increasingly common clinical problem. J Endocrinol 168:353–362

    Article  CAS  PubMed  Google Scholar 

  6. Szuluc P, Munoz F, Claustrat B, Garnero P, Marchand F, Duboeuf F, Delmas PD (2001) Bioavailable estradiol may be an important determinant of osteoporosis in men: the MINOS study. J Clin Endocrinol Metab 86:192–199

    Google Scholar 

  7. Gillberg P, Johansson AG, Ljunghall S (1999) Decreased estradiol levels and free androgen index and elevated sex hormone-binding globulin levels in male idiopathic osteoporosis. Calcif Tissue Int 64:209–213

    Article  CAS  PubMed  Google Scholar 

  8. Carlsen CG, Soerensen TH, Eriksen EF (2000) Prevalence of low serum estradiol levels in male osteoporosis. Osteoporosis Int 11:697–701

    CAS  Google Scholar 

  9. Braidman I, Baris C, Wood L, Selby P, Adams J, Freemont A, Hoyland J (2000) Preliminary evidence for impaired estrogen receptor α-protein expression in osteoblasts and osteocytes from men with idiopathic osteoporosis. Bone 26:423–427

    Article  CAS  PubMed  Google Scholar 

  10. Ongphiphadhanakul B, Rajatanavin R, Chanprasertyothin S, Piaseu N, Chailurkit L (1998) Serum oestradiol and oestrogen receptor gene polymorphism are associated with bone mineral density independently of serum testosterone in normal males. Clin Endocrinol 49:803–809

    Article  CAS  Google Scholar 

  11. Ioannidis JP, Stavrou I, Trikalinos TA, Zois C, Brandi ML, Genari L, Albagha O, Ralston SH, Tsatsoulis A (2002) Association of polymorphisms of the estrogen receptor alpha gene with bone mineral density and fracture risk in women: a meta-analysis. J Bone Miner Res 17:2048–2060

    CAS  PubMed  Google Scholar 

  12. Shearman AM, Karasik D, Gruenthal KM, Demissie S, Cupples A, Housman DE, Kiel DP (2004) Estrogen receptor β polymorphisms are associated with bone mass in women and men: the Framingham study. J Bone Miner Res 19:773–781

    CAS  PubMed  Google Scholar 

  13. Bord S, Ireland DC, Beavan SR, Compston JE (2003) The effects of estrogen on osteoprotegerin, RANKL and estrogen receptor expression in human osteoblasts. Bone 32:136–141

    Article  CAS  PubMed  Google Scholar 

  14. Chen FP, Lee N, Wang KC, Soong YK, Huang KE (2002) Effect of estrogen and 1α,25(OH)2-vitamin D3 on the activity and growth of human osteoblast-like cells in vitro. Fertil Steril 77:1038–1043

    PubMed  Google Scholar 

  15. Liel Y, Kraus S, Levy J, Shany S (1992) Evidence that estrogens modulate activity and increase the number of 1,25-dihydroxyvitamin D receptors in osteoblast-like cells (ROS17/2,8). Endocrinology 130:2597–2601

    Article  CAS  PubMed  Google Scholar 

  16. Duque G, Abdaimi KE, Macoritto M, Miller MM, Kremer R (2002) Estrogens (E2) regulate expression and response of 1,25-dihydroxyvitamin D3 receptors in bone cells: changes with aging and hormone deprivation. Biochem Biophys Res Commun 299:446–454

    Article  CAS  PubMed  Google Scholar 

  17. Johansson AG, Eriksen EF, Lindh E, Langdahl B, Blum WF, Lindahl A, Ljunggren O, Ljunghall S (1997) Reduced serum levels of the growth hormone dependent insulin-like growth factor binding protein and a negative bone balance at the level of individual remodeling units in idiopathic osteoporosis in men. J Clin Endocrinol Metab 82:2795–2798

    Article  CAS  PubMed  Google Scholar 

  18. Kurland ES, Rosen CJ, Cosman F, McMahon D, Chan F, Shane E, Lindsay R, Dempster D, Bilezikian JP (1997) Insulin-like growth factor-I in men with idiopathic osteoporosis. J Clin Endocrinol Metab 82:2799–2805

    Article  CAS  PubMed  Google Scholar 

  19. Lagumdzija A, Oh G, Petersson M, Bucht E, Gonon A, Pernow Y (2004) Inhibited anabolic effect of insulin-like growth factor-I on stromal bone marrow cells in endothelial nitric oxide synthase-knockout mice. Acta Physiol Scand 182:29–35

    Article  CAS  PubMed  Google Scholar 

  20. Lian JB, Stein GS, Aubin JE (2003) Bone formation: maturation and function activities of osteoblast linage cells. In: Primer on the metabolic bone diseases and disorders of mineral metabolism, 5th ed., ASBMR, Washington, DC, pp 13–28

  21. Marie PJ, Sabbagh A, de Vernejoul MC, Lomri A (1989) Osteocalcin and deoxyribonucleic acid synthesis in vitro and histomorphometric indices of bone formation in postmenopausal osteoporosis. J Clin Endocrinol Metab 69:272–279

    CAS  PubMed  Google Scholar 

  22. Marie PJ, Hott M, Launay JM, Graulet AM, Gueris J (1993) In vitro production of cytokines by bone-surface-derived osteoblastic cells in normal and osteoporotic postmenopausal women: relationship with cell proliferation. J Clin Endocrinol Metab 77:824–830

    Article  CAS  PubMed  Google Scholar 

  23. Marie PJ, de Vernejoul MC, Connes D, Hott M (1991) Decreased DNA synthesis by cultured osteoblastic cells in eugonadal osteoporostic men with defective bone formation. J Clin Invest 88:1167–1172

    CAS  PubMed  Google Scholar 

  24. Bang P, Eriksson U, Sara V, Wivall IL, Hall K (1991) Comparison of acid ethanol extraction and acid gel filtration prior to IGF-1 and IGF-2 radioimmunoassays: improvement of determination in acid ethanol extracts by the use of truncated IGF-I as radioligand. Acta Endocrinol (Copenh) 124:620–629

    CAS  Google Scholar 

  25. Hilding A, Hall K, Wivall-Helleryd IL, Sääf M, Melin AL, Thoren M (1999) Serum levels of insulin-like growth factor-I in 152 patients with growth hormone deficiency, aged 19–82 years, in relation to those in healthy subjects. J Clin Endocrinol Metab 84:2013–2019

    Article  CAS  PubMed  Google Scholar 

  26. Povoa G, Roovete A, Hall K (1984) Cross reaction of somatomedin-binding protein a radioimmunoassay developed for somatomedin binding protein isolated from human amniotic fluid. Acta Endocrinol (Copenh) 107:563–570

    CAS  Google Scholar 

  27. Rong H, Hong J, Pernow Y, Sjöstedt U, Bucht E (1997) Quantitation of parathyroid hormone-related protein mRNA by competitive PCR using time-resolved lanthanide fluorometry. Clin Chem 43:2268–2273

    CAS  PubMed  Google Scholar 

  28. Tsai JA, Rong H, Torring O, Matsushita H, Bucht E (2000) Interleukin-1β?upregulates PTHrP-mRNA expression and protein production and decreases TGF-β in normal human osteoblast-like cells. Calcif Tissue Int 66:363–369

    Article  PubMed  Google Scholar 

  29. Mundy GR, Chen D, Oyajobi BO (2003) Bone remodeling. In: Primer on the metabolic bone diseases and disorders of mineral metabolism, 5th ed., ASBMR, Washington, DC, pp 46–58

  30. Gyda M, Corisdeo S, Zaidi M, Troen BR (2001) Macrophage colony stimulating factor suppresses osteoblast formation. Biochem Biophys Res Commun 285:328–334

    Article  CAS  PubMed  Google Scholar 

  31. Katzburg S, Lieberherr M, Ornoy A, Klein BY, Hendel D, Somjen D (1999) Isolation and hormonal responsiveness of primary cultures of human bone-derived cells: gender and age differences. Bone 25:667–673

    Article  CAS  PubMed  Google Scholar 

  32. Martinez P, Moreno I, de Miguel F, Vila V, Esbrit P, Martinez ME (2001) Changes in osteocalcin response to 1,25-dihydroxyvitamin D3 stimulation and basal vitamin D receptor expression in human osteoblastic cells according to donor age and skeletal origin. Bone 29:35–41

    CAS  PubMed  Google Scholar 

  33. Karaplis AC, Goltzman D (2000) Parathyroid hormone and parathyroid hormone-related peptide effects on the skeleton. Rev Endocr Metab Disord 1:331–341

    Article  CAS  PubMed  Google Scholar 

  34. Naves M, Alvarez-Hernandez D, Fernandez-Martin JL, Paz-Jimenez J, Garcia Prado P, Fernandex-Coto T, Santamaria I, Cannata-Andia J (2003) Effect of VDR gene polymorphisms on osteocalcin secretion in calcitriol-stimulated human osteoblasts. Kidney Int Suppl 85:23–27

    Google Scholar 

  35. Van Pottelbergh I, Goemaere S, de Barquer D, de Paepe A, Kaufman M (2002) Vitamin D receptor gene allelic variants, bone density and bone turnover in community-dwelling men. Bone 31:631–637

    PubMed  Google Scholar 

  36. Gomez-Garcia L, Esbrit P, Carrena L, Sabando P, Garcia-Flores M, Martinez ME (2003) Alendronate interacts with the inhibitory effect of 1,25(OH)2D3 on parathyroid hormone-related protein expression in human osteoblastic cells. J Bone Miner Res 18:78–87

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by grants from the Novo Nordic Foundation, Karolinska Institute, Magn Bergwall Foundation, and Stiftelsen Gamla Tjänarinnor. We thank Associate Professor Elisabeth Bucht for the measurement of PTHrP mRNA. We thank Dr. Tycho Tullberg (Stockholm Spine Center) for support and help in finding young control patients.

Author information

Authors and Affiliations

  1. Endocrine and Diabetes Unit, Department of Molecular Medicine, Karolinska Institute and Karolinska University Hospital, Stockholm, S-171 76, Sweden

    Y. Pernow & M. Sääf

  2. Department of Orthopedics, Karolinska Institute and Karolinska University Hospital, Stockholm, S-171 76, Sweden

    B. Granberg & L. Weidenhielm

Authors
  1. Y. Pernow
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Granberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Sääf
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Weidenhielm
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y. Pernow.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pernow, Y., Granberg, B., Sääf, M. et al. Osteoblast Dysfunction in Male Idiopathic Osteoporosis. Calcif Tissue Int 78, 90–97 (2006). https://doi.org/10.1007/s00223-005-0158-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-005-0158-9

Keywords

Search

Navigation